Type 1 diabetes affects more than one million individuals in the United States and many more worldwide. Type 1 diabetes arises in genetically predisposed individuals as a consequence of immune-mediated destruction of the pancreatic islet insulin-secreting beta-cells. The onset of clinical symptoms of diabetes represents the endpoint of a chronic progressive decline in beta-cell function and occurs when the majority of beta-cells have been lost. First-degree relatives of individuals with Type 1 diabetes are ten-fold more likely to develop the disease than the general population. The disease, which can begin at any age, characteristically begins in childhood or in young adults. The present treatment for Type 1 diabetes, which includes the early use of insulin, rigid dietary intervention, and frequent blood glucose monitoring, when implemented properly, can delay or prevent the horrible long-term complications of diabetes (i.e. blindness, renal failure, and amputation). However, proper diabetes treatment is quite difficult to do, expensive, and very invasive to the diabetic patient?s lifestyle. Diabetes is also a major factor in health care costs. Is it possible to prevent Type 1 diabetes? To date, several immune interventions have been tried in genetically susceptible individuals without success. Other trials have been attempted to intervene early in the course of Type 1 diabetes, in order to preserve beta-cell function. These immune interventions have likewise failed. Thus, the identification of agents that either prevent the disease or slow its progression would result in major health care cost savings and reduce complications related to diabetes in addition to the huge individual savings in terms of not having the disease. Our long-term goal is to prevent the development of Type 1 diabetes through the use of innovative immune-based therapies designed to prevent the development of the disease in genetically predisposed individuals. The objectives of this application, in pursuit of that goal and in response to the RFA, is completion of the DPT-1 protocol and the development of TrialNet, an enhanced network to develop and test innovative interventions to prevent or slow the progression of Type 1 diabetes. One such innovative approach to slow the progression of Type 1 diabetes is our proposed pilot protocol, "Thiazolidinediones Preserve C-Peptide in Type 1 Diabetes." The proposed work is innovative because it utilizes a drug that has a proven safety profile and is already widely used for the treatment of Type 2 diabetes but also is an immune modulator. Our Center has the experience, the personnel, and access to the appropriate patients to be a successful member of TrialNet and to be able to successfully complete our proposed pilot protocol or others that TrialNet may bring forward.